IκBNS in tissue regeneration following influenza infection
Role of IκBNS in lung tissue regeneration after influenza A virus infection and its potential impact on lethal synergism between influenza and bacterial pathogens during superinfection
Influenza A virus (IAV) infection are associated with massive and long-term immunopathology in the lung thereby paving the way for bacterial superinfection with often fatal outcome. We recently identified the atypical NF-κB-inhibitory protein IκBNS as a major driver of hyper-inflammation in infected tissues as one of the underlying mechanism for the lethal outcome of a bacterial infection. Besides that, we found that IκBNS-deficiency ameliorates lung inflammation in response to respiratory IAV infection and significantly accelerates tissue regeneration. Ex vivo transcriptional profiling of alveolar epithelial cells (AEC) from lungs of IAV infected wild type mice clearly indicated long-term alterations of the AEC transcriptional program following IAV infection with a striking overexpression of genes involved in tissue remodeling, wound repair and tissue regeneration weeks after infection. Based on these data and the fact that IκBNS is known to be expressed also in non-hematopoietic cells in the lung, we aim to elucidate the role of IκBNS in the inflammatory response of AECs and whether its targeted inactivation would result in improved wound repair and tissue regeneration, which finally would decrease the long-term risk of bacterial superinfection in the IAV infected host.
Prof. Ingo Schmitz, SIME
- Immune Regulation- Prof. Dunja Bruder
- Systems-Oriented Immunology and Inflammation Research- Prof. Dr. Ingo Schmitz
HZI - Helmholtz Centre for Infection Research